Photodynamic therapy is used in the treatment of cancer and other diseases. In this treatment a light absorbing compound (the photosensitiser) is applied to a tumour or other lesion. Subsequently laser light is used to activate the photosensitiser and the tumour tissue is destroyed in a process known as the photodynamic effect.
When the photosensitiser absorbs light it can produce a short-lived but highly active species known as singlet oxygen. Also produced by the activated photosensitiser is superoxide ion, O2−. Singlet oxygen is thought to be the main agent effective against the tumour although the superoxide ion may also participate.
It is believed that the photosensitiser destroys the blood supply to the malignant cells of the tumour, thereby ultimately starving the tumour of oxygen and nutrients. Alternatively, the photosensitiser may cause direct breakdown of tumour cells.
One photosensitiser currently used in PDT is a complex mixture of porphyrins (cyclic tetrapyrroles) known as haematoporphyrin derivative (HpD). A commercial version of HpD is available as Photofrin®. Although approved in various countries for treating various types of tumour, Photofrin has various limitations including the accumulation of the material in the skin for a prolonged period, thereby inducing undesirable photosensitivity under normal daylight.
Various other photosensitisers have been proposed for use in PDT. These include specific porphyrins, phthalocyanines, naphthalocyanines and chlorins. Sulphonated phthalocyanines have been reported to be particularly effective (Rosenthal, I., Photochem. Photobiol., 1991, 53, 859-70.
Photosensitisers may also be used in the diagnosis and detection of medical conditions. For these applications, the photosensitiser is administered to the patient either internally or topically. Abnormal cells take up the photosensitiser to a greater extent than normal cells and, accordingly, when light is applied to the region under investigation an area containing abnormal cells will exhibit greater fluorescence than an area containing only normal cells.
Tetrasulphonylaminoglycine zinc (II) phthalocyanine (TGly) has been described in J. Photochem. Photobiol B: Biology., 45 (1998) 28-35 as a potential agent for PDT. The performance of TGly as a photosensitiser in non-biological situations compared favourably with two clinically used photosensitisers and two others under test. However TGly was relatively poor in its ability to effect haemolysis of red blood cells and would therefore not be considered as a potential agent for use in PDT, diagnosis or detection applied to the human or animal body.
In general, there are various requirements, both chemical and biological, for a useful and clinically effective photosensitiser. The chemical properties include purity, a high quantum yield of singlet oxygen upon activation, the ability to be activated by wavelengths of light in the red to infra-red region (since such radiation penetrates deeply into tissue) and solubility in water. However, sensitisers which satisfy these chemical criteria do not necessarily possess advantageous biological properties for use in clinical PDT. These properties, which include localisation in target tissues (e.g. tumours), lack of skin photosensitivity, rapid clearance from the body and appropriate sub-cellular location are not predictable from chemical structure with current knowledge.